The differential expression of cytosolic carbonic anhydrase in human hepatocellular carcinoma

Kuo, Wu‐Hsien; Chiang, Whei-Ling; Yang, Shun‐Fa; Yeh, Kun‐Tu; Yeh, Chung-Min; Hsieh, Yih‐Shou; Chu, Shu‐Chen

doi:10.1016/s0024-3205(03)00597-6

Cited by 51 publications

(38 citation statements)

References 43 publications

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“…CAIII has two sulfhydryl groups and has been suggested to play a role in scavenging oxygen radicals in cells (Lii et al, 1994;Raisanen et al, 1999). A recent survey of the activities and protein and message levels of CAI, II, and III in 60 HCC patients showed a consistent reduction within the tumors in comparison to the corresponding adjacent normal liver tissues (Kuo et al, 2003). Accordingly, it is possible that CAIII level is lower in the liver tumor than in the adjacent normal tissue in Sod1À/À mice.…”

Section: Discussionmentioning

confidence: 99%

CuZnSOD deficiency leads to persistent and widespread oxidative damage and hepatocarcinogenesis later in life

et al. 2004

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Mice deficient in CuZn superoxide dismutase (CuZn-SOD) showed no overt abnormalities during development and early adulthood, but had a reduced lifespan and increased incidence of neoplastic changes in the liver. Greater than 70% of Sod1À/À mice developed liver nodules that were either nodular hyperplasia or hepatocellular carcinoma (HCC). Cross-sectional studies with livers collected from Sod1À/À and age-matched þ / þ controls revealed extensive oxidative damage in the cytoplasm and, to a lesser extent, in the nucleus and mitochondria from as early as 3 months of age. A marked reduction in cytosolic aconitase, increased levels of 8-oxo dG and F2-isoprostanes, and a moderate reduction in glutathione peroxidase activities and porin levels were observed in all age groups of Sod1À/À mice examined. There were also age-related reductions in Mn superoxide dismutase activities and carbonic anhydrase III. Parallel to the biochemical changes, there were progressive increases in the DNA repair enzyme APEX1, the cell cycle control proteins cyclin D1 and D3, and the hepatocyte growth factor receptor Met. Increased cell proliferation in the presence of persistent oxidative damage to macromolecules likely contributes to hepatocarcinogenesis later in life.

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Section: Discussionmentioning

confidence: 99%

CuZnSOD deficiency leads to persistent and widespread oxidative damage and hepatocarcinogenesis later in life

et al. 2004

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“…Car3 (carbonic anhydrase 3) is suggested to play a role in scavenging oxygen radicals in cells (35,36). The activities, protein levels and message levels of CAR1, 2, and 3 in HCC are consistently reduced in comparison to the corresponding adjacent normal liver tissue (37).…”

Section: Discussionmentioning

confidence: 99%

Gene expression profile of DNA binding protein A transgenic mice

Tobita

Kajino²,

Inami³

et al. 2006

Int J Oncol

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Abstract.We recently reported that the expression of dbpA (DNA binding protein A) is associated with advanced stages of human hepatocellular carcinoma (HCC) and that its transcription is positively regulated by E2F1, which is also implicated in hepatocarcinogenesis. To study the in vivo effect of dbpA on hepatocarcinogenesis, we generated the dbpA-transgenic mouse that specifically expressed a transgene in hepatocytes. Here, we studied the effect of dbpA on the expression of other cellular genes by using microarray analyses. The expression profiles from livers of 31-and 32-week-old male transgenic mice [Tg(+)] that did not show any morphological changes and from livers of their male wild-type littermates [Tg(-)] were compared. Expression differences detected by microarray analyses were validated by reverse transcription-polymerase chain reaction (RT-PCR) using total RNA samples from livers of 3 pairs of Tg(+) and (-) mice. The 11 up-regulated genes included 7 carcinogenesis-related genes (Igfbp1, Tff3, Hpx, Orm2, Ctsl, Plg, Jdp1), and the 9 down-regulated genes included Car3 that is associated with the protection of cells from attack by oxygen radicals. We confirmed that the expression of Igfbp1 (insulin like growth factor binding protein 1) was reduced by siRNA targeting dbpA in the human HCC cell line. In conclusion, our present data suggested that dbpA could be positively involved in carcinogenesis by changing the expression profiles of cellular genes.

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“…Acidic pH in extracellular environment of cancer cells contributes to an aggressive phenotype, which facilitates invasion and metastasis of tumor cells into new target organs. The expression of CA III in human hepatocellular carcinoma (HCC) has been studied by Kuo et al 59 , who discovered that CA I, CA II and CA III protein expression levels are reduced in human HCC cells compared to the adjoining normal tissues. Dai et al 60 , found that the overexpression of CA III results in increased acidity of both extracellular and intracellular environment.…”

Section: Structure and Function Of Ca IIImentioning

confidence: 99%